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Mathematical model for predicting the percutaneous absorption of perfume raw materials.

Cincinnati, OH: University of Cincinnati, 2003 Jan; :1-166
Due to their potential for inducing contact allergy if used improperly, fragrances are carefully assessed for dermal safety prior to incorporation into cosmetic products. Currently, there is no accurate tool for estimating the skin absorption rates and tissue concentrations subsequent to topical exposure of fragrances. This report describes an improved method to estimate the absorption and evaporation of fragrance ingredients from skin, based on their physico-chemical properties. This was accomplished using a first-order kinetic approach expected to be applicable for small topical doses. The rate constants for each compound are functions of temperature T, surface airflow v, and three physico-chemical properties: vapor pressure Pvp, molecular weight MW and lipid solubility Slip. The latter is taken to be the solubility of n-octanol, expressed as the product of octanol/water partition coefficient Koct, and water solubility Sw. Three kinetic models were developed and tested with published fragrance evaporation data on human skin. One of these models was the one-compartment model, in which all dissipation occurs from a skin compartment that rapidly incorporates a topically-applied ingredient. Two alternative models explicitly consider the vehicle layer present in the early stages post-application. Skin disposition of fragrance ingredients in a controlled in vivo study could be satisfactorily correlated with key physico-chemical properties. All three models provided an adequate description of the evaporated fractions. However, the evaporation rate profiles of fixed fragrances were better described by the two-compartment models which yield a biexponential decay. The kinetic models were also tested with the in vitro absorption and evaporation data for benzyl alcohol. Modified Franz diffusion cells fitted with a vapor trap were used to obtain these data. Airflow over the skin surface was controlled in the experiment and accounted for in the model. A linear dependence between airflow and evaporation rate constant(s) was found over the working range of the system, 10-100 mL/min. All three models satisfactorily correlated cumulative absorption and evaporation results. Nevertheless, further details of the evaporation and absorption profiles could be described by means of two-compartment models. Further development of this work may lead to a useful model for dermal exposure assessment for contact allergens.
Skin-exposure; Skin-absorption; Absorption-rates; Chemical-kinetics; Chemical-properties; Dermatology; Dose-response; Exposure-assessment; Exposure-limits; Mathematical-models; Allergies; Allergens; Air-flow
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Research Tools and Approaches: Exposure Assessment Methods
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Mathematical model for predicting the percutaneous absorption of perfume raw materials
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University of Cincinnati
Page last reviewed: February 4, 2022
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